ALBERT

Description: Introduction The oral BTK inhibitor ibrutinib was recently approved for frontline CLL therapy based on RESONATE-2, which included only patients (pts) age ≥65 (Burger et al., 2016). In the absence of comparative data, FCR remains a standard initial therapy for younger CLL pts, particularly in light of recent data suggesting that mutated IGHV predicts long disease free survival after FCR (Thompson et al., 2016, Fischer et al., 2016). However, pts with higher risk CLL such as del(17p) and unmutated IGHVhave less durable responses. Moreover, only about 20% of CLL pts will achieve complete response (CR) with bone marrow minimal residual disease negativity (BM MRD-neg) with frontline FCR (Boettcher et al., 2012). Given the favorable toxicity profile and substantial efficacy of ibrutinib across CLL risk types, we developed an investigator-initiated, multicenter phase II study of ibrutinib plus FCR (iFCR) as frontline treatment for young, fit CLL pts (NCT02251548). Methods The primary objective is to determine the rate of CR with BM MRD-neg in younger CLL pts treated upfront with iFCR. Secondary endpoints include response rate, PFS, and safety/tolerability. Ibrutinib 420 mg daily monotherapy is started 7 days prior to FCR, which is given at standard doses together with ibrutinib for up to 6 cycles. Responders continue on ibrutinib maintenance until progression or unacceptable toxicity. Growth factor support and antimicrobial prophylaxis are mandatory. Eligibility criteria include: age ≤ 65, requiring initial treatment by IW-CLL criteria, ECOG PS ≤1, and adequate organ function. CTCAE v4 and IW-CLL criteria are used to evaluate toxicity and efficacy, with response evaluations after 3 cycles, 2 mos. after final FCR (primary endpoint evaluation), and q6 mos. thereafter. MRD is assessed by 4-color flow cytometry (10-4sensitivity). Results As of August 1, 2016, the study reached full accrual at 35 pts. The median age at enrollment was 55 yrs (range 38-65). 9/33 tested (27%) had del(11q) and 4/33 tested (12%) had del(17p). Unmutated IGHV was present in 20/31 tested (65%), ZAP-70 was positive in 21/32 tested (66%), TP53 mutation was present in 2/31 tested (6%), and NOTCH1 mutation was present in 2/21 tested (10%). We initially enrolled 10 pts in a safety lead-in cohort and did not see any unexpected toxicities. In the entire cohort of 35 pts, hematologic toxicity included grade (gr) 4 neutropenia in 1 pt (3%), as well as gr 3 neutropenia (15%), thrombocytopenia (18%), and anemia (6%). All grade non-hematologic toxicities occurring in 〉15% of pts included nausea (68%), bruising (35%), fatigue (29%), and rash (21%) (all gr 1/2) and diarrhea (21%) (all gr 1). The only bleeding events were gr 1 epistaxis in 2 pts. SAEs included gr 4 febrile neutropenia, gr 3 atrial fibrillation, gr 3 transaminitis, gr 3 pneumonia, and gr 3 appendicitis in 1 pt each. 9% of pts experienced ≥gr 3 infection. A median of 6 cycles of FCR were given (range 3-6). One pt had ibrutinib dose reduction (pt with febrile neutropenia), and 18% of pts had at least 1 dose reduction of chemotherapy. Twenty-eight pts have undergone primary endpoint re-staging after completing the iFCR combination and 26 pts have been tested for BM MRD. In these 26 pts, the rate of CR with BM MRD-neg is 39% (10/26). In the 28 pts with re-staging, the ORR is 100%, including 39% (11/28) with CR or CRi. 17/28 (61%) pts had a PR, and all 17 PR pts have residual lymph nodes ≤ 2.5 cm in long axis by CT imaging. BM was MRD-neg in 23/26 tested (89%), including 13/17 (76%) of pts in PR. With a median follow-up of 12.1 months (range 0.1-21.1), all pts are alive, and 33 of the 35 pts remain on treatment. One pt who completed 6 cycles of iFCR and achieved CR with BM MRD-neg declined ibrutinib maintenance and remains in MRD-neg CR at 10 months off therapy, and one pt with del(17p) achieved MRD-pos PR and elected to pursue allogeneic stem cell transplant. Conclusions iFCR induces deep responses in previously untreated young CLL pts, with 39% of evaluable pts achieving CR with BM-MRD-neg and 89% achieving BM MRD-neg, significantly higher than the 20% rate seen historically with FCR alone. Low rates of hematologic and infectious toxicities were observed, possibly due to mandatory use of growth factor support and antimicrobial prophylaxis. 76% of PR pts have achieved BM MRD-neg, and all of these pts have small residual lymph nodes. Pts continue on ibrutinib maintenance and will be monitored for conversion to CR with BM MRD-neg. over time. Disclosures Davids: Genentech: Consultancy, Honoraria, Research Funding; Infinity: Honoraria, Research Funding; Janssen: Consultancy, Honoraria; Gilead: Honoraria; Abbvie: Consultancy, Honoraria; Pharmacyclics: Consultancy, Honoraria, Research Funding; TG Therapeutics: Honoraria, Research Funding. Brander:TG Therapeutics: Research Funding; Gilead: Honoraria. Jacobson:Kite: Membership on an entity's Board of Directors or advisory committees. Abramson:Gilead: Consultancy; Abbvie: Consultancy; Seattle Genetics: Consultancy; Kite Pharma: Consultancy. Fisher:Pharmacyclics: Consultancy. Brown:Acetylon, Gilead: Research Funding; Celgene, Roche/Genentech, Gilead, Infinity, Janssen, Pharmacyclics, ProNai, Sun BioPharma: Consultancy.

Description: Abstract 2496 Poster Board II-473 Background: HMG-CoA reductase inhibitors (statins) have been used to treat hypercholesterolemia and hyperlipidemia for over 20 years. Statins competitively inhibit HMG-CoA reductase thereby blocking the synthesis of mevalonate. They directly inhibit synthesis of steroid hormones and cholesterol but also indirectly inhibit prenylation and ubiqitination. As all currently marketed statins are lipophillic, with the exception of Pravachol (pravastatin), several therapeutic trials have attempted to exploit these indirect actions to treat both neoplastic (glioblastoma, anaplastic astrocytoma) and degenerative (Alzheimer's, Parkinson's) neurologic disease. We studied the impact of incidentally prescribed statins on high-risk patients with primary central nervous system diffuse large B cell lymphoma (PCNSL). Methods: We used an IRB-approved clinicopathologic database, derived from comprehensive tumor registry data at the Massachusetts General Hospital, to identify all patients diagnosed with primary central nervous system lymphoma (PCNSL) between 1991 and 2007 (n=118). We excluded pediatric patients, patients who did not receive curative treatment and patients who failed to achieve a CR with initial therapy. Automated analysis of billing and medication administration records was used to identify the administration of statins to these patients. We compared the outcome of patients who were receiving statins to controls with PCNSL who did not receive statins. We excluded patients who did not receive statins within the time interval from 6 months prior to 2 years after their PCNSL diagnosis. As only a single statin pt was less than 50 we excluded all pts below this age from the cases and controls. All patients received high dose MTX based therapy. Overall survival (OS) was calculated from the date of first methotrexate. Results: Median age of statin patients was 66 yrs (range 52 – 76); median age of controls was 66 years (range 50 - 86). Nine patients were on atorvastatin, 9 were on simvastatin, 1 each were on pravastatin, rosuvastatin and fluvastatin. At a median follow-up of 47.5 months, concurrent statin therapy was associated with improved OS (62% vs. 37%)(p=0.04 Log-rank test). The median OS for all statin patients 〉 50 years old (n=21) was 60 months versus 37 months for all other patients 〉 50 years old (n=67) (p=

Description: Background Studies from the chemoimmunotherapy (CIT) era and more recently with venetoclax have demonstrated the correlation between minimal residual disease (MRD) response measured by at least four-color flow cytometry (FC), and progression free (PFS) and overall survival (OS) in CLL. Despite high overall (ORR) and complete (CR) response rates observed with fludarabine-based combination CIT, the ability to achieve sustained undetectable MRD (uMRD) remission is lacking for the majority of patients treated with these regimens. We have previously reported on the promising combination of ibrutinib plus FCR (iFCR), which demonstrated a 98.8% ORR, 32.9% CR/CRi with bone marrow (BM) uMRD at EOT, and 77.7% BM-uMRD by flow at EOT (83.5% at best response) [Davids et al, Lancet Haematology, 2019]. Adaptive's next generation sequencing (NGS)-MRD assay targets immunoglobulin receptor sequencing with up to 10E-6 sensitivity for detection of B-cell malignancies. Here we present expanded MRD analysis by standard flow cytometry and the first results assessed using NGS-MRD, focusing on mid-FCR (C3) and 2 month post-FCR (EOT) timepoints. Methods iFCR is a multicenter single-arm phase 2 trial at seven sites in the USA. 85 patients aged 65 years or younger with previously untreated CLL were enrolled and treated with iFCR as previously published [Davids, Lancet Haematology, 2019]. Per protocol analyses of MRD in both peripheral blood (PB) and BM by standard four-color FC were performed at local laboratories at C3. Both PB and BM samples were submitted to Adaptive for NGS-MRD evaluation at EOT. Forty-eight patients had paired BM and PB samples with 16 additional PB only samples. NGS-MRD status was evaluated at 10E-5 and 10E-6 levels, and defined as positive if ≥ 1 rearrangement was detected per 100,000 or per million cells, respectively. An indeterminate finding was reported if insufficient cells were assayed, as NGS-MRD testing is limited by the number of cells evaluated, which can often be lower than needed for 10E-6 sensitivity, particularly in PB. Results At the C3 restage, the BM-uMRD rate by flow was 47%, with 100% concordance to flow PB-uMRD status in all patients with BM-uMRD. However, 33% (12/36 evaluable) with detectable cells in marrow had PB-uMRD, demonstrating enhanced sensitivity of BM-MRD testing as shown in Table 1. At EOT, BM-uMRD rates rose to 78%, compared with 86% in PB, including 14/24 patients converted from BM-pos/PB-pos to BM-neg/PB-neg and 7/12 BM-pos/PB-neg to BM-neg/PB-neg. In NGS-MRD analysis from 48 patients with evaluable BM and PB samples at EOT, a larger number of patients were MRD positive in BM (n=21; 43.8%) vs. PB (n=13; 27.1%) (McNemar test: p=0.04). Figure 1 illustrates the improving detection of residual disease in both BM and PB with increasing sensitivity, with greater detection in BM; 54% positive at 10E-6 sensitivity in this cohort, compared with 36% in PB. Evaluation for true negative samples at 10E-6 sensitivity was limited by samples with inadequate cells for evaluation (indeterminate), hence definite uMRD was seen in only 23% BM and 9% PB. Fifty-two patients with PB-uMRD by FC at EOT had associated PB NGS-MRD results: 10 PB-uMRD by FC were positive at 10E-5 with 8 additional positive at 10E-6 (35% greater than FC). Similar results were observed in BM: of forty-four patients with BM-uMRD by FC at EOT, 13 were positive at 10E-5 with 9 additional positive at 10E-6 by NGS-MRD (50% greater than FC), summarized in Table 2. When this higher sensitivity BM-uMRD data is used to define overall clinical response at EOT, the CR/CRi with BM-uMRD rate at 10E-5 is 32.6% (14/43), and at 10E-6 is 16.2% (6/37), compared to 43.8% (21/48) using four-color FC. The rate of BM-uMRD would be 60.5% (26/43) at 10E-5 sensitivity and 29.7% (11/37) at 10E-6, with NGS-MRD. Discussion This first report of NGS-MRD testing after iFCR demonstrates that 50% of patients with BM-uMRD by flow cytometry have detectable CLL cells at the level of detection of ≥ 1 per million cells. While iFCR has improved upon historical uMRD results by four-color flow cytometry, these findings suggest that CLL cells are still frequently present. Longer follow-up will be required to correlate these minimal levels of residual disease with PFS in this setting. Future studies should incorporate NGS-MRD assessment with larger volume cell sampling to ensure adequate sensitivity and evaluate venetoclax-based regimens. Disclosures Brander: Novartis: Consultancy; BeiGene: Research Funding; DTRM Biopharma: Research Funding; AbbVie: Consultancy, Honoraria, Research Funding; Pharmacyclics LLC, an AbbVie Company: Consultancy; MEI: Research Funding; Acerta: Research Funding; Tolero: Research Funding; Teva: Consultancy, Honoraria; TG Therapeutics: Consultancy, Honoraria, Research Funding; Genentech: Consultancy, Honoraria, Research Funding; AstraZeneca: Consultancy, Research Funding. Jacob:Adaptive Biotechnologies: Employment, Other: shareholder. Arnason:Regeneron Pharmaceuticals, Inc.: Consultancy; Celgene/Juno: Consultancy. Abramson:AbbVie Inc, Amgen Inc, Bayer HealthCare Pharmaceuticals, Celgene Corporation, EMD Serono Inc, Genentech, Gilead Sciences Inc, Janssen Biotech Inc, Juno Therapeutics, a Celgene Company, Karyopharm Therapeutics, Kite Pharma Inc, Merck, Novartis, Seattle Gen: Consultancy. Davids:AbbVie, Acerta Pharma, Adaptive, Biotechnologies, Astra-Zeneca, Genentech, Gilead Sciences, Janssen, Pharmacyclics, TG therapeutics: Membership on an entity's Board of Directors or advisory committees; Acerta Pharma, Ascentage Pharma, Genentech, MEI pharma, Pharmacyclics, Surface Oncology, TG Therapeutics, Verastem: Research Funding; AbbVie, Astra-Zeneca, Genentech, Janssen, MEI, Pharmacyclics, Syros Pharmaceuticals, Verastem: Consultancy; Research to Practice: Honoraria. Brown:Novartis: Consultancy; Sunesis: Consultancy; Acerta Pharma: Consultancy; AstraZeneca: Consultancy; BeiGene: Consultancy; Catapult Therapeutics: Consultancy; Dynamo Therapeutics: Consultancy; Genentech/Roche: Consultancy; Gilead: Consultancy, Research Funding; Juno/Celgene: Consultancy; Pfizer: Consultancy; Loxo: Consultancy, Research Funding; Invectys: Other: Data safety monitoring board; Octapharma: Consultancy; Kite, a Gilead Company: Consultancy, Research Funding; AbbVie: Consultancy; Morphosys: Other: Data safety monitoring board; Pharmacyclics: Consultancy; Teva: Honoraria; TG Therapeutics: Consultancy; Verastem: Consultancy, Research Funding; Sun Pharmaceuticals: Research Funding; Janssen: Honoraria.

Description: Burkitt lymphoma (BL) is a highly aggressive B-cell non-Hodgkin lymphoma (NHL) accounting for nearly 3% of all newly diagnosed NHLs. Treatment of adult non-HIV-related BL with the intensive CODOX-M/IVAC regimen (modified Magrath regimen) produces complete responses (CR) in 75 to 86% of patients, with lower CR rates reported in HIV-related BL. The CD20-directed monoclonal antibody rituximab has never been reported in combination with CODOX-M/IVAC, and here we report the first series in BL patients, with or without HIV infection. A total of 24 patients were identified at our institutions who received rituximab plus CODOX-M/IVAC with curative intent. Rituximab was administered at 375mg/m2 on day 3 of cycle 1, and then on day 1 of subsequent cycles. Twenty-three patients received 4 alternating cycles of R-CODOX-M/R-IVAC for high risk disease, while 1 patient received 3 cycles of R-CODOX-M alone for low risk disease, defined as a single focus less than 10cm with a normal LDH. All patients received white cell growth factor support, and pneumocystis prophylaxis was included for all HIV+ patients. The median age was 45 years (17–67), advanced Ann Arbor stage 80%, LDH 〉 upper limit of normal 80%, extra nodal involvement 80% and ECOG PS

Description: BACKGROUND: ABVD with or without radiation is standard therapy for limited stage HL, but carries risks of bleomycin-lung injury and radiation toxicity. Brentuximab vedotin (BV) is an anti-CD30 antibody drug conjugate which is highly active in relapsed classical HL. We previously combined BV with AVD in limited stage non-bulky classical HL which resulted in a high CR rate, but at the cost of increased neutropenia, neutropenic fever, and neuropathy, likely related to the overlapping toxicity profile with vinblastine. Similar toxicity findings were also observed with BV-AVD in advanced stage classical Hodgkin lymphoma. We therefore evaluated BV plus AD (BV-AD) without radiation therapy for non-bulky stage I-II classical HL with the goal of reducing toxicity and maintaining high rates of inducing CR. METHODS: This is a multicenter single arm open label phase 2 study. Patients received BV 1.2 mg/kg plus standard dose adriamycin and dacarbazine on days 1 and 15 of each 28 day cycle. GCSF prophylaxis was not included. Patients received 4 or 6 cycles of BV-AD based on the results of an interim PETCT scan performed following cycle 2. PET negativity was defined as Deauville scores 1-3. Patients in CR on interim PETCT received 4 total cycles of therapy; patients in PR completed 6 cycles. The primary endpoint is complete response rate (CRR) at end of treatment. A sample size of 34 was required to detect an end of treatment CRR of 95% with 91% power and alpha error of 0.09. RESULTS: 34 patients were enrolled. Median age is 36 (range 18-63). Stage is IA (3), IB (1), IIA (29) and IIB (1). Risk is classified per the GHSG criteria as early unfavorable in 47%, and favorable in 53%. The interim CR rate is 94%. Accordingly, 32 interim PET negative patients (94%) received 4 total cycles of therapy, and 2 interim PET positive patients (6%) received 6 total cycles of therapy. No patients received consolidative radiation therapy, per protocol. The primary endpoint of end of treatment CR rate is 100%. At a median follow-up of 15 months, the FFS, PFS and OS are all 100%. The most common adverse events of any grade are nausea (79%), peripheral sensory neuropathy (56%), fatigue (50%), constipation (38%), alopecia (35%) and neutropenia (24%). Most toxicities were low grade, with only 15% of subjects experiencing any grade 3 toxicity, and there were no grade 4 or 5 toxicities. Specifically, 2 patients had grade 3 neutropenia, and 1 patient each had grade 3 nausea/vomiting, pneumonia and thromboembolic event. Peripheral sensory neuropathy was grade 1 in 17 patients, and grade 2 in 2 patients. There were no cases of neutropenic fever. CONCLUSIONS: BV-AD for 4-6 cycles induces high interim and end of treatment CR rates of 94% and 100%, respectively, allowing 4 total cycles of therapy in most patients. The PFS, FFS and OS are all 100% at last follow up. Toxicity appears mild and notable for a low incidence of neutropenia, alopecia, and moderate peripheral neuropathy. This promising regimen avoids bleomycin, vinblastine, radiation and primary GCSF prophylaxis with resultant low toxicity and preserved high efficacy rates in patients with early favorable and early unfavorable non-bulky limited stage classical Hodgkin lymphoma. Follow up for this trial is ongoing. Figure. Figure. Disclosures Abramson: Merck: Consultancy; Seattle Genetics: Consultancy; Karyopharm: Consultancy; Verastem: Consultancy; Amgen: Consultancy; Humanigen: Consultancy; Juno Therapeutics: Consultancy; Gilead: Consultancy; Novartis: Consultancy; Bayer: Consultancy; Celgene: Consultancy. Sokol:Mallinckrodt Pharmaceuticals: Consultancy; Seattle Genetics: Consultancy; Spectrum Pharmaceuticals: Consultancy. Jacobsen:Merck: Consultancy; Seattle Genetics: Consultancy. LaCasce:Seattle Genetics: Consultancy, Honoraria; Research to Practice: Speakers Bureau; Humanigen: Consultancy, Honoraria; Bristol-Myers Squibb: Other: Data safety and monitoring board.

Description: INTRODUCTION: Information on the differential resources and costs associated with managing treatment-related adverse events (TRAEs) from chimeric antigen receptor T-cell (CAR T) therapies, including cytokine release syndrome (CRS), have not been estimated and may differ by therapy. Lisocabtagene maraleucel (liso-cel; JCAR017) is a CD19-directed 4-1BB CAR T cell product administered in a defined composition at a precise 1:1 dose of CD8 and CD4 CAR T cells. TRANSCEND-NHL 001 is a multicenter seamless design pivotal phase 1 trial of liso-cel in R/R B-NHL (NCT02631044). The objectives of this analysis were to estimate the cost of CRS management observed in the TRANSCEND-NHL trial and to compare the CRS treatment with the trial's management guidelines. METHODS: Case report forms detailed health resource utilization (HRU) related to CRS management among patients treated in the TRANSCEND-NHL trial who experienced CRS. CRS was graded per Lee et al. 2014. A two-step micro-costing method was used to identify resource use and estimate costs associated with CRS. Step 1 included analyzing HRU for managing each event, including number of inpatient days, number of intensive care unit (ICU) days, procedures (e.g. lab work, imaging, biopsy), and medications. HRU that occurred within the TRAE onset date and resolution date was included. Step 2 involved applying costs to each HRU. The base-case analysis included only HRU collected among patients from the TRANSCEND-NHL trial that was in accordance with trial's CRS management guidelines for each specified grade. Scenario analysis included HRU not specified in the guidelines. Unit costs were from the health system perspective and were adjusted to 2018 USD. Cost per inpatient day ($2,668) was estimated from HCUP Databases, and cost per ICU day ($6,546) was sourced from Dasta et al. 2005. Medication cost data are from REDBOOKTM using wholesale acquisition cost. Diagnostic and procedure costs are from the Centers for Medicare & Medicaid Services lab fee schedule and physician fee schedule, respectively. Analyses are stratified by grade and by site of care (inpatient or outpatient) at which the CAR T cell therapy was administered. RESULTS: CRS occurred in 38 of 102 patients treated in the dose-finding/dose-expansion portions of the TRANSCEND-NHL clinical trial. Among the 38 patients, 19 patients experienced grade 1, 18 grade 2, and 1 grade 4 CRS. Total HRU and cost differed between CRS grades. Length of stay (LOS) associated with CRS management by grade are shown in Table 1. Median and average LOS increased with higher CRS grades. Mean LOS for grades 1 and 2 were 4 and 7 days, respectively. One patient with grade 4 had a 34-day LOS. No patients with CRS grade 1 were transferred to the ICU, and the mean ICU LOS for CRS grade 2 patients was 1 day. Mean LOS was longer among patients who were administered CAR T therapy in the inpatient setting (6.3 days) compared with the outpatient setting (5.3 days). Patients in TRANSCEND-NHL were successfully managed with conservative health resource utilization compared with the guidelines. For instance, while the trial management guidelines suggest tocilizumab for patients with Grade 2 CRS, this was administered to only half of Grade 2 CRS patients (9/18, 50%). Total cost is driven by LOS and for grades 1 and 2 CRS ranged from $11,226 to $25,617. LOS represented 94.4% and 83.5% of total cost in grades 1 and 2, respectively. The one CRS grade 4 patient incurred a 34-day LOS, contributing 94.9% of an estimated total cost of $201,836. Resource use not referenced in the guidelines was largely comprised of medication use and resulted in minimal increases in total cost. Costs due to resource use outside of the guidelines ranged from $1,698 to $21,055. The total cost of CRS management is reported in Figure 1. CONCLUSIONS: The results of this analysis show that hospital and ICU LOS are key drivers of CRS management cost and are mainly associated with managing grade 3/4 CRS. These results are based on national average costs; actual costs may vary between hospitals. The incidence of CRS and management guidelines vary across CAR T therapies and will affect both HRU and associated cost differences. CRS management is also contingent on patient characteristics. The biology of CAR Ts and resultant safety profile of the various products will likely drive dissimilarities in CRS management and cost. Disclosures Siddiqi: Juno Therapeutics: Other: Steering committee. Garcia:Juno Therapeutics, a fully owned subsidiary of Celgene: Employment, Equity Ownership. Dehner:Juno Therapeutics, a fully owned subsidiary of Celgene: Employment, Equity Ownership. Nguyen:Juno Therapeutics: Consultancy. Gitlin:Juno Therapeutics: Consultancy. Chung:Juno Therapeutics: Employment. Abramson:Verastem: Consultancy; Amgen: Consultancy; Novartis: Consultancy; Bayer: Consultancy; Juno Therapeutics: Consultancy; Gilead: Consultancy; Celgene: Consultancy; Karyopharm: Consultancy; Merck: Consultancy; Humanigen: Consultancy; Seattle Genetics: Consultancy.

Description: Key Points A subset of DHL patients may be cured, and some patients may benefit from intensive induction. Further investigations into the roles of SCT and novel agents are needed.

Description: Abstract 3716 Background: Rituximab monotherapy as initial treatment for low-grade B-cell lymphomas produces responses in approximately 70% of patients with one third achieving a complete response, and progression-free survival (PFS) of approximately 2 years. Maintenance rituximab appears to prolong initial remissions after rituximab alone. Current dosing for rituximab is largely empiric, so we sought to investigate whether increased doses of rituximab induction would increase the complete response rate (CRR) over that expected from standard dose rituximab. We also sought to assess whether high-dose induction followed by standard maintenance would produce a PFS comparable with that of combination chemoimmunotherapy strategies. Methods: We conducted a phase II trial of increased-dose rituximab monotherapy induction, followed by a standard maintenance schedule. Eligible patients were adults with previously untreated low-grade B-cell lymphomas with measurable disease 〉2cm and were not candidates for potentially curative radiotherapy to localized disease. Subjects were treated with induction rituximab at a dose of 750 mg/m2 on days 1,8,15, and 22. Patients without progressive disease were then treated with maintenance rituximab at 375mg/m2 every 3 months for 8 doses or until disease progression. The primary end point was CRR as defined by the International Workshop Response Criteria (1999). Secondary endpoints included overall response rate (ORR), PFS, and toxicity. The study was designed with 90% power to show a 50% CRR, with a 30% CRR considered unworthy of further study. Results: Between August 2009 and August 2010, 40 eligible subjects were enrolled (31 grade 1–2 follicular lymphomas, 4 marginal zone lymphomas, 3 small lymphocytic lymphomas, and 2 indolent B cell lymphoma not otherwise specified). The median age was 60 (range 36–88) All subjects had advanced Ann Arbor stage disease. Twenty-two subjects (55%) had involvement of 〉4 nodal sites, 6 (15%) had a Hgb

Description: The standard treatment for limited-stage Hodgkin lymphoma has been combined modality therapy, but late toxicities of radiation have prompted investigation of chemotherapy alone in low risk patients. Initial trials have demonstrated a small increased risk of relapse if radiation is omitted, but no difference in overall survival. We investigated the predictive value of interim FDG-PET (PET) scans in nonbulky limited stage patients, and asked whether PET may guide the use of consolidative radiotherapy for patients in complete remission after chemotherapy alone. A total of 68 patients with nonbulky limited stage disease were identified at our institutions with interim PET performed after 2–3 cycles of chemotherapy. All patients received anthracycline-based chemotherapy with curative intent. PET scan interpretations were extracted by chart review of radiology reports. The median age was 35 (range 18–77). Fifty-nine patients had disease in the neck and mediastinum, 6 had inguinal disease, and 2 in Waldeyer’s ring. Fifty-two patients were stage IIA, 4 were IIB, 10 were IA, and 1 was IB. Radiation was included at the discretion of the treating physician. Complete response required a negative PET scan. The complete response (CR) rate was 88%. Fifty-one patients (75%) had a negative interim PET, and 17 (25%) had a positive interim PET. Interim PET− patients were more likely to achieve a CR at the end of therapy compared to interim PET+ patients (98% vs. 59%; p=0.0001, Fisher’s exact test). At a median follow up of 32 months (range 3–70), the progression-free (PFS) and overall survival (OS) for the entire series were 85% and 100%, respectively. Interim PET− patients had an improved PFS compared to PET+ patients (90% vs. 71%; p=0.032, log rank test). Among the 60 patients who achieved a CR, 50 (83%) were interim PET−, and 10 (17%) were interim PET+. There was no difference in PFS between interim PET+ and PET− patients who achieved a CR. The most important predictor of PFS was achievement of CR at the end of therapy (92% vs. 37%; p